Endocrine Abstracts

Background: Hypercalcemia is a well-described paraneoplastic manifestation encountered in a variety of malignancies. However, it is rarely the initial feature of a neuroendocrine tumor.

Herein we report a caseof metastatic pancreatic neuroendocrine tumor (NET)presenting with a refractory hypercalcemia and initially misdiagnosed as an adenocarcinoma of the pancreas.

Objective: The aim of this case report is to illustratesome of thecomplexities pertaining to the diagnosis of a pancreatic NET and the challenges in the management of an associated hypercalcemia caused by parathyroid hormone related protein (PTHrP) hypersecretion.

Clinical case and results: A 67-year-old woman presented with asthenia and weight loss and was found to have severe hypercalcemia. Laboratory evaluation demonstrated high calcium levels associated with low serum parathyroid hormone (PTH) levels. Despite an initial low PTHrP level, nephrogenous cAMP was elevated consistent with PTHrP related hypercalcemia. Work up revealed a pancreatic tumor associated with liver and splenic metastases but no bone metastases. Biopsy of the liver metastasis concluded to an adenocarcinoma and appropriate chemotherapy was initiated. Despite the stability of the pancreatic tumor, the associated hypercalcemia was refractory to various supportive therapy and chemotherapeutic regimens including corticosteroids, bisphosphonates, calcitonin and denosumab. Because of the indolent progression of the tumor and in view of the persistent hypercalcemia, slides of the pancreatic tumor were reviewed, and complementary immunohistochemistry was performed. The results contradicted the initial diagnosis and were compatible with a well differentiated pancreatic NET. Additional staining was positive for PTHrP confirming the secretion of this hormone by the tumor. Chemoembolization of the liver metastases was performed and treatment with somatostatin analogues (SSA) was introduced allowing a good but transient control of the hypercalcemia. This phenomenon of tachyphylaxis, occurring after a few months of therapy with SSAs, has been described in some patients with NETs. Due to the rise of calcium levels, the patient was referred for vectorized internal radiation therapy.

Conclusion: We report a case of pancreatic NET with hypercalcemia as a presenting feature initially misdiagnosed as adenocarcinoma. Hypercalcemia was refractory to all symptomatic therapies and was transiently controlled with SSA. This case highlights the challenges in diagnosing and controlling hypercalcemia due to PTHrP hypersecretion in patients with NETs. Furthermore, it underlines the importance of reconsidering the initial diagnosis in front of an unusual course of the disease.